We have encountered a uniform rcp (11:22) translocation in Ewing's sarcoma. This is true of all lines and tumors examined to date (equivalent to 20). It is not true of neuroblastoma, lymphoma, or soft tissue sarcoma. Interestingly, it is also present in a unique childhood tumor, peripheral neuroepithelioma and the closely related chest wall tumor described by Askin et al., the so-called Askin tumor. The break point on chromosome 22 is close to a known oncogene, c-sis. No amplification or rearrangement of c-sis has been detected. In the case of peripheral neuroepitelioma, c-sis is not amplified, but c-myc is. Unlike classic neuroblastoma, N-myc is not expressed. These results serve to emphasize the common abnormality found in Ewing's sarcoma, its distinction from other round cell tumors, and the unique character of peripheral neuroepithelioma.